The lead programme in Vernalis' cough cold pipeline, Tuzistra® XR, was approved by the FDA in April 2015 for the relief of cough and symptoms associated with upper respiratory allergies or a common cold in adults 18 years of age and older.

Description

Tuzistra XR (codeine polistirex and chlorpheniramine polistirex) extended-release oral suspension, CIII, is the first product from Vernalis' development and licensing deal with Tris to be approved by FDA.

Proof-of-concept was achieved in March 2013, with the pivotal single dose and multi dose bioavailability studies completed by February 2014. The NDA was submitted to FDA in June 2014 and approval granted on 30 April 2015.

Tris supplies the product to Vernalis and Vernalis is commercialising throughout the US prescription cough cold market.

Product Information

Tuzistra XR (codeine polistirex and chlorpheniramine polistirex) extended-release oral suspension is a Schedule III (CIII) DEA controlled drug that has been approved by the FDA:

• for the relief of cough and symptoms associated with upper respiratory allergies or a common cold in adults 18 years of age and older• Important Limitations of Use: Not indicated for pediatric patients under 18 years of age.

Tuzistra XR is administered as an oral dose of 10mL every 12 hours and may be taken with or without food.

Like other codeine-containing products, Tuzistra XR has a Boxed Warning relating to the use of codeine in children and concomitant use with CNS depressants.

IMPORTANT SAFETY INFORMATION

WARNING

ULTRA-RAPID METABOLISM OF CODEINE AND OTHER RISK FACTORS FOR LIFE-THREATENING RESPIRATORY DEPRESSION IN CHILDREN

Life-threatening respiratory depression and death have occurred in children who received codeine; most cases followed tonsillectomy and/or adenoidectomy and many of the children had evidence of being an ultra-rapid metabolizer of codeine due to a CYP2D6 polymorphism.

TUZISTRA XR is contraindicated in children younger than 12 years of age and in children younger than 18 years of age following tonsillectomy and/or adenoidectomy. Avoid the use of TUZISTRA XR in adolescents 12 to 18 years of age who have other risk factors that may increase their sensitivity to the respiratory depressant effects of codeine.

RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS

Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Avoid use of opioid cough medications in patients taking benzodiazepines, other CNS depressants, or alcohol.

IMPORTANT RISK INFORMATION

What is the most important information I should know about TUZISTRA® XR?

TUZISTRA XR can cause children to stop breathing (respiratory depression) and cause death.

Do not give TUZISTRA XR to children younger than 12 years of age, or to children younger than 18 years of age after tonsillectomy or adenoidectomy surgery.

You should not give TUZISTRA XR to children between 12 to 18 years of age who have certain risk factors for breathing problems, including:

recent surgery

obstructive sleep apnea

are obese

severe lung problems

other medical conditions that can cause difficulty breathing, such as neuromuscular problems

taking other medicines that cause breathing problems

You should not breastfeed during treatment with TUZISTRA XR because it may cause your child to stop breathing and cause death.

Severe drowsiness, breathing problems (respiratory depression), coma, and death can happen in adults and children who take TUZISTRA XR with benzodiazepines, or other central nervous system depressants, including alcohol.

Avoid taking other medicines that can cause drowsiness or sleepiness, or drinking alcohol during treatment with TUZISTRA XR. Ask your healthcare provider for a list of these medicines if you are not sure.

Take TUZISTRA XR exactly as prescribed by your healthcare provider. If you take the wrong dose of TUZISTRA XR, you could overdose and die. See the Medication Guide section called “How should I take TUZISTRA XR?” for important information about how to take TUZISTRA XR correctly.

Avoid driving a car or operating machinery during treatment with TUZISTRA XR.

Call your healthcare provider or get emergency medical help right away if anyone taking TUZISTRA XR, or your breastfeeding baby has any of the symptoms listed below:

increased sleepiness

shallow breathing

confusion

limpness

difficulty breathing

your baby has difficulty breastfeeding

Keep TUZISTRA XR in a safe place away from children. Accidental use by a child is a medical emergency and can cause death. If a child accidentally takes TUZISTRA XR, get emergency help right away.

What is TUZISTRA XR?

TUZISTRA XR (two-zis-tra) is a prescription medicine used to treat cough and respiratory symptoms that you can have with allergies or a common cold. TUZISTRA XR contains 2 medicines, codeine and chlorpheniramine. Codeine is a narcotic cough suppressant. Chlorpheniramine is an antihistamine.

TUZISTRA XR is a federal controlled substance (C-III) because it contains codeine that can be abused or lead to dependence. Keep TUZISTRA XR in a safe place to prevent misuse and abuse. Selling or giving away TUZISTRA XR may harm others, and it is against the law. Tell your healthcare provider if you have abused or been dependent on alcohol, prescription medicines or street drugs.

TUZISTRA XR is not for children under 18 years of age. It is not known if TUZISTRA XR is safe and effective in children under 18 years of age.

Who should not take TUZISTRA XR?

Do not give TUZISTRA XR to any children younger than 12 years of age.

Do not give TUZISTRA XR to children younger than 18 years of age after tonsillectomy or adenoidectomy surgery.

Do not take TUZISTRA XR if you are allergic to any of the ingredients in TUZISTRA XR.

What should I tell my healthcare professional before taking TUZISTRA XR?

Before you take TUZISTRA XR, tell your healthcare professional about all your medical conditions, including if you:

have a drug dependence

have problems with your urinary tract (urethral stricture)

have lung or breathing problems

plan to have surgery

have had a head injury, drink alcohol, have pain in your stomach-area (abdomen), kidney or liver problems, a history of severe or persistent cough, diabetes, prostate or thyroid problems, such as hypothyroidism

are pregnant or plan to become pregnant. It is not known if TUZISTRA XR will harm your unborn baby. You and your healthcare provider should decide if you should take TUZISTRA XR while you are pregnant.

are breastfeeding or plan to breastfeed. Codeine and chlorpheniramine pass into your breast milk and may harm your baby. You should not breastfeed during treatment with TUZISTRA XR.

Tell your healthcare professional about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Taking TUZISTRA XR with certain other medicines can cause side effects or affect how well TUZISTRA XR or the other medicines work. Do not start or stop other medicines without talking to your healthcare provider. Especially tell your healthcare professional if you:

take pain medicines such as narcotics

take cold or allergy medicines that contain antihistamines or cough suppressants

take medicines for mental illness (anti-psychotics, anti-anxiety)

drink alcohol

take medicines for depression, including monoamine oxidase inhibitors (MAOIs)

take medicines for stomach or intestine problemsAsk your healthcare provider if you are not sure if you take one of these medicines.

How should I take TUZISTRA XR?

Take TUZISTRA XR exactly as your healthcare provider tells you.

Your healthcare provider will tell you how much TUZISTRA XR to take and when to take it. Do not change your dose without talking to your healthcare provider.

TUZISTRA XR is usually taken every 12 hours.

Do not take more than 20 mL of TUZISTRA XR in 24 hours.

Take TUZISTRA XR by mouth only.

Shake the TUZISTRA XR bottle well before you use it.

TUZISTRA XR can be taken with or without food.

Do not mix TUZISTRA XR with other fluids or medicines.

TUZISTRA XR should be taken using an accurate milliliter measuring device.

Ask your pharmacist to give you a measuring device to help you measure the correct amount of TUZISTRA XR. Do not use a household teaspoon to measure your medicine. You may accidently take too much.

If you take too much TUZISTRA XR, call your healthcare provider or go to the nearest hospital emergency room right away.

What should I avoid doing while taking TUZISTRA XR?

TUZISTRA XR can cause you to be drowsy. Avoid driving a car or using machinery during treatment with TUZISTRA XR.

Avoid drinking alcohol during treatment with TUZISTRA XR. Drinking alcohol can increase your chances of having serious side effects.

What are the possible side effects of TUZISTRA XR?

TUZISTRA XR may cause serious side effects, including:

See “What is the most important information I should know about TUZISTRA XR?”

Breathing problems (respiratory depression), which can lead to death. Call your healthcare provider or get emergency treatment right away if you have excessive sleepiness, shallow or slow breathing, or confusion.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the TUZISTRA XR Medication Guide before you start taking TUZISTRA XR and each time you get a refill, as there may be changes. This information does not take the place of talking to your healthcare professional about your medical condition or treatment.